Dichlorobis(cyclopentadienyl)zirconium1

[1291-32-3]  · C10H10Cl2Zr  · Dichlorobis(cyclopentadienyl)zirconium  · (MW 292.32)

(good starting material to prepare many kinds of zirconocene(II or IV) derivatives;2 in combination with organometallics (Al, Zn, or Mg) it is a catalyst for stereo- and regioselective alkylation of unsaturated compounds;3 in combination with an AgI salt (AgX; X = ClO4, OTf, BF4) it is an effective activator for glycosyl fluorides; in combination with MAO, it is a good catalyst for polymer synthesis4)

Physical Data: mp 247-249 °C; sublimes at 150-180 °C.

Solubility: sol aromatic solvents, chloroform; slightly sol THF, ether; insol hexanes.

Form Supplied in: colorless crystals; widely available.

Analysis of Reagent Purity: 1H NMR (THF-d8) d 6.62 (s, C5H5).

Handling, Storage, and Precautions: the dry solid is reasonably stable to air and moisture and can be handled in the ordinary manner. However, it should be stored in a tightly sealed nitrogen-flushed bottle.

Hydrozirconating Agent.

Cp2ZrCl2 is a very important starting material for the preparation of ZrIV and ZrII derivatives. Cp2ZrCl2 is a key compound for the preparation of the so called Schwartz reagent (Chlorobis(cyclopentadienyl)hydridozirconium),5 which is a versatile hydrozirconating agent. Among the methods for reduction of Cp2ZrCl2,6 an economical method for the isolation (eq 1)7 and a method for the generation8 of Cp2ZrHCl in situ (eq 2) are recommended for organic synthesis.

Transmetalation.

Transmetalation of Cp2ZrCl2 with organometallics containing lithium, sodium, potassium, and magnesium appears to be a general method to prepare Cp2ZrR2 (R =alkyl, allyl, benzyl, alkenyl, aryl, and alkynyl). The reaction of 1 mol of organometallic with 1 mol of Cp2ZrCl2 to produce Cp2ZrRCl requires precise reaction conditions and judicious choice of organometallic to avoid the formation of Cp2ZrR2 (eq 3). One example of the importance of reaction conditions and the ligand to obtain a Cp2ZrRCl-type compound is seen in a contrasting pair of reactions (eqs 4 and 5).9

Carbometalation Catalyst.

In a valuable synthetic transformation, stereo- and regioselective addition of organometallics to unsaturated compounds can be catalyzed by Cp2ZrCl2 to give carbometalated compounds. Reaction of terminal or internal alkynes with organoaluminum in the presence of Cp2ZrCl2 gives the syn addition products (>98%) in good to excellent yields (eq 6).10 The reactions of terminal alkynes with Trimethylaluminum are regioselective, with the addition of the methyl group to the internal carbon (95%), but the regioselectivity drops to the 75-85% range for other alkyl groups. Although addition of organozinc can also be catalyzed by Cp2ZrCl2, higher yields are obtained using Cp2ZrI2 (eq 7).11 These regio- and stereoselective carbometalations have been applied to the synthesis of natural products.12 Interestingly, in the Cp2ZrCl2-catalyzed carboalumination, the addition of 1-2 equiv of water to the reaction mixture significantly increases the rate of the carboalumination.13 The effect of the added water is considered to be due to formation of an oxo-bridged dimer and not to formation of methylaluminoxane, which is a cocatalyst for the polymerization of a-alkenes. When an alkyl group of R3Al has b-hydrogens, hydroalumination via hydrozirconation becomes a serious side reaction.14 It can, however, be suppressed by the use of the R2AlCl-Cp2ZrCl2 reagent system. With i-Bu3Al and Cp2ZrCl2, a clean hydroalumination is observed.15

Carbometalation of alkenes catalyzed by Cp2ZrCl2 proceeds using aluminum (eq 8) and/or magnesium reagents (eq 9). The carbomagnesation reaction of alkenes is known to proceed through a totally different process from that of the carboalumination of alkynes (eq 10).16 That is, prior formation of a zirconocene-ethylene complex by the reaction of Cp2ZrCl2 with Ethylmagnesium Bromide and the subsequent coupling reaction with vinyl compounds has been confirmed. The stereochemistry and rate of ethyl magnesation are influenced by the presence of an allylic or homoallylic oxygen functionality (eqs 11 and 12).17

Generation of Cp2Zr and its Equivalent.

Generation of Cp2Zr can be achieved by reduction of Cp2ZrCl2 with Magnesium-Mercury(II) Chloride (eq 13)18 or 2 equiv n-Butyllithium (eq 14).19 The latter method is recommended since the metal reduction of Cp2ZrCl2 is prone to a side reaction leading to ZrIII species.20 Low valent ZrII generated with 2 equiv n-BuLi exists as a Cp2Zr-butene complex (eq 15). The Cp2Zr-butene complex reacts with a series of unsaturated compounds (alkynes, alkenes,10b,21 imines,22 and azadienes23) through a ligand exchange process to give the desired zirconocene complexes (eqs 16 and 17). Therefore the Cp2Zr-butene complex is often called zirconocene equivalent (Cp2Zr). When the reaction of Cp2Zr with an unsaturated compound is hampered by the presence of the butene, which is released in situ by ligand exchange, use of t-Butyllithium instead of n-BuLi is recommended.24 The isobutene generated in situ by ligand exchange in the modified procedure is much less reactive than butene toward the Cp2Zr-substrate complex. The Cp2Zr equivalent is largely applied to bicyclizations of nonconjugated dienes, enynes, and/or diynes (eq 18).21 These Cp2Zr-promoted cyclizations, which proceed with high regio- and stereoselectivity,25 have been applied to the syntheses of many natural products.26

Apart from the Cp2Zr-mediated cyclization chemistry, various allylic zirconium derivatives can be generated from allylic ethers and Cp2Zr (eq 19).27 This process is a result of the initial formation of zirconacyclopropane and the subsequent elimination of a b-alkoxyl group. In a similar way, the generation of allenic28 and g-alkoxyallylic29 zirconium has been achieved from propargylic ethers and acrolein diethyl acetal, respectively. Allylic zirconium derivatives can also be generated in situ by the metal-exchange reaction of allylic Grignard reagents with Cp2ZrCl2.30 The reactivity of these allylic or allenic zirconium species towards carbonyl compounds is much larger than that of other alkyl zirconocene derivatives. In general, the nucleophilic reactivity of the organozirconium compound having a cyclopentadienyl ligand is low. The Cp2ZrCl2/2 mol n-BuLi reagent, which generates the zirconocene equivalent in situ, is also applicable as a efficient catalyst in the hydrosilylation of alkenes,31 Tishchenko reaction32 of aldehydes, and a cross-aromatization of cyclohexanone derivatives.33

Zirconium Enolate.

Cp2ZrCl2 is often used to generate very important metal enolates. Zirconocene enolates generated in situ from lithium enolates of carbonyl compounds play a very important role in the stereoselectivity of the products in the crossed aldol reaction (eq 20)34 and [2,3]-Wittig rearrangements (eq 21).35 In the aldol reactions a zirconium enolate reacts with carbonyl compounds to give aldol products in a highly erythro selective manner regardless of the geometry of the enolate. The rationale for the excellent selectivity in these reactions can be explained by the s-bond angle, geometry of the coordination site, and the oxophilic nature of zirconocene(IV) derivatives.36

Glycosidation.

The combination of Cp2ZrCl2 and a silver salt (AgX, X = ClO4, OTf, and BF4) is a highly effective reagent system for activating glycosyl fluoride to give the O-37 or C-glycoside38 stereoselectively under very mild conditions (eq 22). This activation process is presumed to involve a cationic zirconocene species as an actual activator (eq 23) and has been applied to the synthesis of a natural product.37

Methylenation of Carbonyls.

The methylenation of carbonyls (aldehydes, ketones, and enones) is effectively carried out by treating the carbonyls with Cp2ZrCl2, CH2X2 (X = Cl or Br), and Zinc powder (eqs 24 and 25).39 This system is presumed to form a bimetallic complex. This bimetallic complex attacks the carbonyl compound to afford metallaoxacyclobutane, which rapidly collapses to zirconocene oxide and the methylenated product (eq 26). Unlike the Tebbe reagent (m-Chlorobis(cyclopentadienyl)(dimethylaluminum)-m-methylenetitanium),40 this zirconium system does not successfully methylenate esters and lactones.

Polymerization Catalyst.

Another important application of Cp2ZrCl2 as a catalyst is found in polymer chemistry. The combination of Cp2ZrCl2 and methylaluminoxane (MAO) is a famous system (Ziegler-type system) for polymerization of ethylene to polyethylene.41

Related Reagents.

Chlorobis(cyclopentadienyl)hydridozirconium; Dichlorobis(cyclopentadienyl)titanium; Dichlorobis(cyclopentadienyl)zirconium-Silver(I) Salts; Dichlorobis(cyclopentadienyl)zirconium-Zinc-Dibromomethane.


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Takeo Taguchi & Yuji Hanzawa

Tokyo College of Pharmacy, Japan



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